Highly Efficient Biosynthesis of <i>γ</i>-Bisabolene with a New Sesquiterpene Synthase AcTPS5 by Dual Cytoplasmic-Peroxisomal Engineering in <i>Saccharomyces cerevisiae</i>
<i>γ</i>-bisabolene is a monocyclic sesquiterpene with various biological activities; it has also been approved as a food additive. Additionally, the hydrogenated form of bisabolene is considered as a potential alternative to D2 diesel. <i>Saccharomyces cerevisiae</i> has the...
| Main Authors: | , , , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
MDPI AG
2023-08-01
|
| Series: | Fermentation |
| Subjects: | |
| Online Access: | https://www.mdpi.com/2311-5637/9/9/779 |
| _version_ | 1797580160025755648 |
|---|---|
| author | Jiajia Liu Ge Yao Xiukun Wan Fuli Wang Penggang Han Shaoheng Bao Kang Wang Tianyu Song Hui Jiang |
| author_facet | Jiajia Liu Ge Yao Xiukun Wan Fuli Wang Penggang Han Shaoheng Bao Kang Wang Tianyu Song Hui Jiang |
| author_sort | Jiajia Liu |
| collection | DOAJ |
| description | <i>γ</i>-bisabolene is a monocyclic sesquiterpene with various biological activities; it has also been approved as a food additive. Additionally, the hydrogenated form of bisabolene is considered as a potential alternative to D2 diesel. <i>Saccharomyces cerevisiae</i> has the ability to produce a large amount of acetyl-CoA in both cytosol and peroxisomes, which serves as a precursor in terpene biosynthesis. In this study, AcTPS5 was identified as a new <i>γ</i>-bisabolene synthase. By expressing AcTPS5 and the mevalonate pathway in peroxisomes, <i>γ</i>-bisabolene titer was achieved at 125.0 mg/L. Deleting the peroxisome autophagy gene <i>atg36</i> further improved <i>γ</i>-bisabolene production to 216.9 mg/L. The implementation of dual cytoplasmic–peroxisomal engineering further boosted <i>γ</i>-bisabolene production to 296.4 mg/L. Finally, through increasing the acetyl-CoA supply and down-regulating the expression of <i>ERG9</i>, <i>γ</i>-bisabolene production was achieved at 584.14 mg/L in shake-flask fermentation and 2.69 g/L in fed-batch fermentation, which is the highest reported production of <i>γ</i>-bisabolene to date. The strategy presented in this study provides an efficient approach for terpene production in <i>S. cerevisiae</i>. |
| first_indexed | 2024-03-10T22:46:25Z |
| format | Article |
| id | doaj.art-868e94309c6946f48b6f078bf45fd9e1 |
| institution | Directory Open Access Journal |
| issn | 2311-5637 |
| language | English |
| last_indexed | 2024-03-10T22:46:25Z |
| publishDate | 2023-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Fermentation |
| spelling | doaj.art-868e94309c6946f48b6f078bf45fd9e12023-11-19T10:38:25ZengMDPI AGFermentation2311-56372023-08-019977910.3390/fermentation9090779Highly Efficient Biosynthesis of <i>γ</i>-Bisabolene with a New Sesquiterpene Synthase AcTPS5 by Dual Cytoplasmic-Peroxisomal Engineering in <i>Saccharomyces cerevisiae</i>Jiajia Liu0Ge Yao1Xiukun Wan2Fuli Wang3Penggang Han4Shaoheng Bao5Kang Wang6Tianyu Song7Hui Jiang8State Key Laboratory of NBC Protection for Civilian, Beijing 102205, ChinaState Key Laboratory of NBC Protection for Civilian, Beijing 102205, ChinaState Key Laboratory of NBC Protection for Civilian, Beijing 102205, ChinaState Key Laboratory of NBC Protection for Civilian, Beijing 102205, ChinaState Key Laboratory of NBC Protection for Civilian, Beijing 102205, ChinaState Key Laboratory of NBC Protection for Civilian, Beijing 102205, ChinaState Key Laboratory of NBC Protection for Civilian, Beijing 102205, ChinaState Key Laboratory of NBC Protection for Civilian, Beijing 102205, ChinaState Key Laboratory of NBC Protection for Civilian, Beijing 102205, China<i>γ</i>-bisabolene is a monocyclic sesquiterpene with various biological activities; it has also been approved as a food additive. Additionally, the hydrogenated form of bisabolene is considered as a potential alternative to D2 diesel. <i>Saccharomyces cerevisiae</i> has the ability to produce a large amount of acetyl-CoA in both cytosol and peroxisomes, which serves as a precursor in terpene biosynthesis. In this study, AcTPS5 was identified as a new <i>γ</i>-bisabolene synthase. By expressing AcTPS5 and the mevalonate pathway in peroxisomes, <i>γ</i>-bisabolene titer was achieved at 125.0 mg/L. Deleting the peroxisome autophagy gene <i>atg36</i> further improved <i>γ</i>-bisabolene production to 216.9 mg/L. The implementation of dual cytoplasmic–peroxisomal engineering further boosted <i>γ</i>-bisabolene production to 296.4 mg/L. Finally, through increasing the acetyl-CoA supply and down-regulating the expression of <i>ERG9</i>, <i>γ</i>-bisabolene production was achieved at 584.14 mg/L in shake-flask fermentation and 2.69 g/L in fed-batch fermentation, which is the highest reported production of <i>γ</i>-bisabolene to date. The strategy presented in this study provides an efficient approach for terpene production in <i>S. cerevisiae</i>.https://www.mdpi.com/2311-5637/9/9/779<i>γ</i>-bisaboleneperoxisomemetabolic engineering<i>Saccharomyces cerevisiae</i> |
| spellingShingle | Jiajia Liu Ge Yao Xiukun Wan Fuli Wang Penggang Han Shaoheng Bao Kang Wang Tianyu Song Hui Jiang Highly Efficient Biosynthesis of <i>γ</i>-Bisabolene with a New Sesquiterpene Synthase AcTPS5 by Dual Cytoplasmic-Peroxisomal Engineering in <i>Saccharomyces cerevisiae</i> Fermentation <i>γ</i>-bisabolene peroxisome metabolic engineering <i>Saccharomyces cerevisiae</i> |
| title | Highly Efficient Biosynthesis of <i>γ</i>-Bisabolene with a New Sesquiterpene Synthase AcTPS5 by Dual Cytoplasmic-Peroxisomal Engineering in <i>Saccharomyces cerevisiae</i> |
| title_full | Highly Efficient Biosynthesis of <i>γ</i>-Bisabolene with a New Sesquiterpene Synthase AcTPS5 by Dual Cytoplasmic-Peroxisomal Engineering in <i>Saccharomyces cerevisiae</i> |
| title_fullStr | Highly Efficient Biosynthesis of <i>γ</i>-Bisabolene with a New Sesquiterpene Synthase AcTPS5 by Dual Cytoplasmic-Peroxisomal Engineering in <i>Saccharomyces cerevisiae</i> |
| title_full_unstemmed | Highly Efficient Biosynthesis of <i>γ</i>-Bisabolene with a New Sesquiterpene Synthase AcTPS5 by Dual Cytoplasmic-Peroxisomal Engineering in <i>Saccharomyces cerevisiae</i> |
| title_short | Highly Efficient Biosynthesis of <i>γ</i>-Bisabolene with a New Sesquiterpene Synthase AcTPS5 by Dual Cytoplasmic-Peroxisomal Engineering in <i>Saccharomyces cerevisiae</i> |
| title_sort | highly efficient biosynthesis of i γ i bisabolene with a new sesquiterpene synthase actps5 by dual cytoplasmic peroxisomal engineering in i saccharomyces cerevisiae i |
| topic | <i>γ</i>-bisabolene peroxisome metabolic engineering <i>Saccharomyces cerevisiae</i> |
| url | https://www.mdpi.com/2311-5637/9/9/779 |
| work_keys_str_mv | AT jiajialiu highlyefficientbiosynthesisofigibisabolenewithanewsesquiterpenesynthaseactps5bydualcytoplasmicperoxisomalengineeringinisaccharomycescerevisiaei AT geyao highlyefficientbiosynthesisofigibisabolenewithanewsesquiterpenesynthaseactps5bydualcytoplasmicperoxisomalengineeringinisaccharomycescerevisiaei AT xiukunwan highlyefficientbiosynthesisofigibisabolenewithanewsesquiterpenesynthaseactps5bydualcytoplasmicperoxisomalengineeringinisaccharomycescerevisiaei AT fuliwang highlyefficientbiosynthesisofigibisabolenewithanewsesquiterpenesynthaseactps5bydualcytoplasmicperoxisomalengineeringinisaccharomycescerevisiaei AT pengganghan highlyefficientbiosynthesisofigibisabolenewithanewsesquiterpenesynthaseactps5bydualcytoplasmicperoxisomalengineeringinisaccharomycescerevisiaei AT shaohengbao highlyefficientbiosynthesisofigibisabolenewithanewsesquiterpenesynthaseactps5bydualcytoplasmicperoxisomalengineeringinisaccharomycescerevisiaei AT kangwang highlyefficientbiosynthesisofigibisabolenewithanewsesquiterpenesynthaseactps5bydualcytoplasmicperoxisomalengineeringinisaccharomycescerevisiaei AT tianyusong highlyefficientbiosynthesisofigibisabolenewithanewsesquiterpenesynthaseactps5bydualcytoplasmicperoxisomalengineeringinisaccharomycescerevisiaei AT huijiang highlyefficientbiosynthesisofigibisabolenewithanewsesquiterpenesynthaseactps5bydualcytoplasmicperoxisomalengineeringinisaccharomycescerevisiaei |